INTRASUBJECT VARIABILITY IN AIRWAY INFLAMMATION IN BIOPSIES IN MILD-TO-MODERATE STABLE ASTHMA

We have studied intrasubject variability with respect to counts of imm unostained inflammatory cells in snap frozen endobronchial biopsies fr om a group of patients with clinically mild to moderate stable asthma. Fiberoptic bronchoscopy was used to obtain endobronchial biopsies fro m the upper and lower lobes in 12 volunteer subjects with asthma on tw o separate occasions 1 mo apart. During this period there was no signi ficant change in asthma treatment, symptom scores, pulmonary function, or airway hyperresponsiveness. With the aid of immunohistochemistry a nd interactive image analysis, subepithelial counts for T lymphocytes, T-lymphocyte subsets, and eosinophils were made. There was wide intra subject variability between anatomic site and with time for all the in flammatory cell counts. In each case the intrasubject variability with time was greater than lobar differences. Power calculations were made to establish the optimal sample size required for each marker. We con clude that even in stable asthma considerable biologic variability com pounds sampling variability. Such sources of variability need to be bo rne in mind when calculating the likely power of intervention studies using biopsy data as end points. Power calculations suggest that appro ximately 15 subjects would be an optimal number with little advantage in increasing beyond this.